TY - JOUR
T1 - The AD tau core spontaneously self-assembles and recruits full-length tau to filaments
AU - Carlomagno, Yari
AU - Manne, Sireesha
AU - DeTure, Michael
AU - Prudencio, Mercedes
AU - Zhang, Yong Jie
AU - Hanna Al-Shaikh, Rana
AU - Dunmore, Judith A.
AU - Daughrity, Lillian M.
AU - Song, Yuping
AU - Castanedes-Casey, Monica
AU - Lewis-Tuffin, Laura J.
AU - Nicholson, Katharine A.
AU - Wszolek, Zbigniew K.
AU - Dickson, Dennis W.
AU - Fitzpatrick, Anthony W.P.
AU - Petrucelli, Leonard
AU - Cook, Casey N.
N1 - Publisher Copyright:
© 2021 The Authors
PY - 2021/3/16
Y1 - 2021/3/16
N2 - Tau accumulation is a major pathological hallmark of Alzheimer's disease (AD) and other tauopathies, but the mechanism(s) of tau aggregation remains unclear. Taking advantage of the identification of tau filament cores by cryoelectron microscopy, we demonstrate that the AD tau core possesses the intrinsic ability to spontaneously aggregate in the absence of an inducer, with antibodies generated against AD tau core filaments detecting AD tau pathology. The AD tau core also drives aggregation of full-length wild-type tau, increases seeding potential, and templates abnormal forms of tau present in brain homogenates and antemortem cerebrospinal fluid (CSF) from patients with AD in an ultrasensitive real-time quaking-induced conversion (QuIC) assay. Finally, we show that the filament cores in corticobasal degeneration (CBD) and Pick's disease (PiD) similarly assemble into filaments under physiological conditions. These results document an approach to modeling tau aggregation and have significant implications for in vivo investigation of tau transmission and biomarker development.
AB - Tau accumulation is a major pathological hallmark of Alzheimer's disease (AD) and other tauopathies, but the mechanism(s) of tau aggregation remains unclear. Taking advantage of the identification of tau filament cores by cryoelectron microscopy, we demonstrate that the AD tau core possesses the intrinsic ability to spontaneously aggregate in the absence of an inducer, with antibodies generated against AD tau core filaments detecting AD tau pathology. The AD tau core also drives aggregation of full-length wild-type tau, increases seeding potential, and templates abnormal forms of tau present in brain homogenates and antemortem cerebrospinal fluid (CSF) from patients with AD in an ultrasensitive real-time quaking-induced conversion (QuIC) assay. Finally, we show that the filament cores in corticobasal degeneration (CBD) and Pick's disease (PiD) similarly assemble into filaments under physiological conditions. These results document an approach to modeling tau aggregation and have significant implications for in vivo investigation of tau transmission and biomarker development.
KW - Alzheimer's disease
KW - Pick's disease
KW - aggregation
KW - biomarker
KW - corticobasal degeneration
KW - filament core
KW - neurofibrillary tangles
KW - real-time quaking-induced conversion
KW - tau
KW - tauopathy
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U2 - 10.1016/j.celrep.2021.108843
DO - 10.1016/j.celrep.2021.108843
M3 - Article
C2 - 33730588
AN - SCOPUS:85102596049
SN - 2211-1247
VL - 34
JO - Cell reports
JF - Cell reports
IS - 11
M1 - 108843
ER -